{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T19:27:28Z","timestamp":1757705248361},"reference-count":0,"publisher":"American Diabetes Association","issue":"5","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1997,5,1]]},"abstract":"<jats:p>The overworked\u2013\u03b2-cell hypothesis proposes that lowered glucose-potentiated insulin secretory responses in diabetes are secondary to hyperstimulated insulin secretion and depletion of the \u03b2-cell insulin stores. We tested this hypothesis in normal rats using a 48-h infusion of 200 mg \u00b7 kg\u22121 \u00b7 day\u22121 tolbutamide in 20% glucose. Insulin secretion was measured by in vitro pancreas perfusion. Twice daily blood glucose values were equal in the tolbutamide-infused and control rats. Pancreas insulin content was 47 \u00b1 7% that of the controls (P &amp;lt; 0.004). Insulin responses to 16.7 mmol\/l glucose, 16.7 mmol\/l glucose\/10 mmol\/l arginine, and 5.5 mmol\/l glucose\/ 10 mmol\/l arginine were reduced in parallel, except for the first phase response to 16.7 mmol\/l glucose\/arginine. Pancreas amylin content was unchanged in the tolbutamide-infused rats as was amylin secretion, resulting in higher than normal stored and secreted amylin-to-insulin molar ratios. Importantly, a raised amylin-to-insulin ratio and a relatively unimpaired first versus second phase insulin response for high glucose\/arginine both occur in diabetic rats. Thus, our results support the overworked\u2013\u03b2-cell hypothesis by showing chronic \u03b2-cell stimulation without hyperglycemia replicates part of the \u03b2-cell dysfunction found with diabetes.<\/jats:p>","DOI":"10.2337\/diab.46.5.808","type":"journal-article","created":{"date-parts":[[2013,9,19]],"date-time":"2013-09-19T17:42:54Z","timestamp":1379612574000},"page":"808-813","update-policy":"http:\/\/dx.doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":18,"title":["Parallel Reduction of Pancreas Insulin Content and Insulin Secretion in 48-h Tolbutamide-Infused Normoglycemic Rats"],"prefix":"10.2337","volume":"46","author":[{"given":"Y A","family":"Hosokawa","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Diabetes Mellitus, and Molecular Medicine, New England Medical Center, and Tuft's University School of Medicine\u2008Boston, MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jack L","family":"Leahy","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes Mellitus, and Molecular Medicine, New England Medical Center, and Tuft's University School of Medicine\u2008Boston, MA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1167","container-title":["Diabetes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.org\/diabetes\/diabetes\/article-pdf\/46\/5\/808\/362995\/46-5-808.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article-pdf\/46\/5\/808\/362995\/46-5-808.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T16:33:21Z","timestamp":1667406801000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article\/46\/5\/808\/9819\/Parallel-Reduction-of-Pancreas-Insulin-Content-and"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1997,5,1]]},"references-count":0,"journal-issue":{"issue":"5","published-print":{"date-parts":[[1997,5,1]]}},"URL":"https:\/\/doi.org\/10.2337\/diab.46.5.808","relation":{},"ISSN":["0012-1797","1939-327X"],"issn-type":[{"value":"0012-1797","type":"print"},{"value":"1939-327X","type":"electronic"}],"subject":[],"published":{"date-parts":[[1997,5,1]]}}}